The activity and expression of adenylosuccinate lyase were reduced during modern human evolution, affecting brain and behavior.

ABSTRACT: Adenylosuccinate lyase (ADSL), an enzyme that is crucial for purine biosynthesis, carries an amino acid substitution that is present in almost all humans today but absent in Neandertals and Denisovans. This substitution reduces the stability of the enzyme, but what functional consequences it has are unknown. Here, we show that when introduced into mice, this substitution causes substrates of the enzyme to accumulate in amounts that correlate negatively with ADSL expression levels. In the brain, where the expression of the enzyme is low, the substitution results in particularly high substrate levels. When the behavior of the mice is analyzed, female mice expressing the modern human-like version of ADSL access water more efficiently for drinking than their wild-type littermates. In addition

SUBMITTER: Ju XC 

PROVIDER: S-EPMC12358879 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature